Method of treating behavioral disorders

ABSTRACT

The present invention provides a method of treating behavioral disorders such as attention deficit hyperactivity disorder, comprising administering an effective amount of (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine or a pharmaceutically acceptable salt thereof to a patient in need thereof and the like.

FIELD OF THE INVENTION

The present invention relates to a method of treating behavioraldisorders such as attention deficit hyperactivity disorder.

BACKGROUND OF THE INVENTION

Attention deficit hyperactivity disorder (“ADHD”) is a behavioraldisorder commonly diagnosed in childhood, estimated to affect 2 to 9.5percent of all school-age children worldwide. One half to two thirds ofthese children will continue to suffer into adulthood. Its core symptomsinclude developmentally inappropriate levels of attention,concentration, activity, distractibility, and impulsivity. ADHD is thuscharacterized by hyperactive motor behavior, decreased attention span,impulsiveness and a variety of cognitive and perceptual problems.Children with ADHD usually have functional impairment across multiplesettings including home, school, and peer relationships. ADHD has alsobeen shown to have long-term adverse effects on academic performance,vocational success, and social-emotional development.

The direct and immediate causes of ADHD have not been known yet.Neurological imaging studies suggest involvement of the prefrontalcortex, part of the cerebellum, and at least two of the clusters ofnerve cells deep in the brain that are collectively known as the basalganglia. The right prefrontal cortex, two basal ganglia called thecaudate nucleus and the globus pallidus, and the vermis region of thecerebellum were found to be significantly smaller than normal inchildren with ADHD (Scientific American, pp. 66-71, September 1998). Thebrain areas that are reduced in size in children with ADHD are the veryones that regulate attention. Genetics can contribute to ADHD. ADHD riskof a child whose identical twin has the disorder is 11 to 18 timesgreater than that of a nontwin sibling of a child with ADHD. Mutationsin several genes that are normally very active in the prefrontal cortexand basal ganglia have been suggested to play a role in structuralshrinking of the brain areas in ADHD. Particular variations in dopaminetransporter gene, DAT 1, and dopamine receptor gene D4 were found morelikely in children with ADHD (Scientific American, pp. 66-71, September1998). Adenosine A_(2A) receptor polymorphisms have also been reportedin ADHD [Clinical Genetics, 58, pp. 31-40 (2000)].

Despite progress in the assessment, diagnosis, and treatment of childrenand adults with ADHD, the disorder has remained controversial. One ofthe major controversies regarding ADHD concerns the use ofpsychostimulants to treat the condition. Psychostimulants, includingamphetamine, methylphenidate, and pemoline, are by far the most widelyresearched and commonly prescribed treatments for ADHD [NationalInstitutes of Health Consensus Development Conference Statement 1998Nov. 16-18; 16(2): 1-37]. Because psychostimulants are more readilyavailable and are being prescribed more frequently, concerns haveintensified over their potential overuse and abuse. Very high doses ofpsychostimulants, particularly of amphetamines, may cause centralnervous system damage, cardiovascular damage, and hypertension. Inaddition, high doses have been associated with compulsive behaviors and,in certain vulnerable individuals, movement disorders. There is a rarepercentage of children and adults treated at high doses who havehallucinogenic responses. Drugs used for ADHD other thanpsychostimulants have their own adverse reactions: tricyclicantidepressants may induce cardiac arrhythmias, bupropion at high dosescan cause seizures, and pemoline is associated with liver damage[National Institutes of Health Consensus Development ConferenceStatement 1998 Nov. 16-18; 16(2): 1-37]. Thus, efficacious and saferprophylactic or therapeutic agents of ADHD are needed.

Tic/Tourette's disorder is described in the Diagnostic and StatisticalManual of Mental Disorders (Fourth Edition—Revised, 1994, published bythe American Psychiatric Association, Washington, D.C., U.S.A., pp.100-105). Tic/Tourette's disorder is a behavioral disorder commonlydiagnosed in childhood or adolescence, estimated to affect 4 to 5individuals per 10,000, and it is reported that this disorder isapproximately 1.5 to 3 times more common in males than in females. Thefollowing four disorders are included in Tic/Tourette's disorder:Tourette's disorder, chronic motor or vocal tic disorder, transient ticdisorder, and tic disorder not otherwise specified.

A tic is a sudden, rapid, recurrent, nonrythmic, stereotyped motormovement or vocalization, and the symptoms are irresistible but can besuppressed after a lapse of time. All forms of tics may be exacerbatedby stress and attenuated during absorbing activities.

The essential features of Tourette's disorder are multiple motor ticsand one or more vocal tics. These features may appear simultaneously orseparately.

The age at the onset of Tourette's disorder may be as early as age 2, isusually during childhood or early adolescence, and is by definitionbefore age 18. The median age at the onset of motor tic is 7 years. Theduration of the disorder is usually lifelong, though periods ofremission lasting from weeks to years may occur. In most cases, theseverity, frequency, and variability of the symptoms diminish duringadolescence and adulthood. In other cases, the symptoms disappearentirely, usually by early adulthood.

Frequently comorbid with Tourette's disorder, ADHD has prevalence of20-90 percent within clinic populations (Kaplan & Sadock's ComprehensiveTextbook of Psychiatry, seventh edition, 2000, Lippincott Williams &Wilkins, Philadelphia).

The vulnerability to Tourette's disorder and related disorders istransmitted in an autosomal dominant pattern.

The major form of treatment of Tic/Tourette's disorder continues to bebased on high-potency “typical” neuroleptics (tiaprid, pimozide,haloperidol, and the like), which may induce a wide range of potentiallyserious side effects.

WO 99/12546 discloses that some xanthine derivatives have an inhibitoryaction on neurodegeneration and are useful as a therapeutic agent forneurodegenerative disorders such as Alzheimer's disease, progressivesupranuclear palsy, AIDS brain fever, propagating spongy brain fever,Huntington's chorea, multiple sclerosis, amyotrophic lateral sclerosis(ALS), multi-system atrophy, brain ischemia, and attention deficithyperactivity disorder.

SUMMARY OF THE INVENTION

The object of the present invention is to provide an excellent method oftreating behavioral disorders such as attention deficit hyperactivitydisorder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the effect of Compound (I) on locomotoractivity in 6-hydroxydopamine-treated or vehicle-treated rats. * meansP<0.05 compared with vehicle-treated rats. CI means Compound (I).

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the following (1) to (9).

-   -   (1) A method of treating a behavioral disorder, comprising        administering an effective amount of        (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine        [hereinafter referred to as Compound (I)] or a pharmaceutically        acceptable salt thereof to a patient in need thereof.    -   (2) Use of Compound (I) or a pharmaceutically acceptable salt        thereof for manufacturing a therapeutic agent for the treatment        of a behavioral disorder.    -   (3) A therapeutic agent for a behavioral disorder comprising        Compound (I) or a pharmaceutically acceptable salt thereof.    -   (4) The method of treating a behavioral disorder according to        the above (1), wherein the behavioral disorder is attention        deficit hyperactivity disorder.    -   (5) The use according to the above (2), wherein the behavioral        disorder is attention deficit hyperactivity disorder.    -   (6) The therapeutic agent for a behavioral disorder according to        the above (3), wherein the behavioral disorder is attention        deficit hyperactivity disorder.    -   (7) The method of treating a behavioral disorder according to        the above (1), wherein the behavioral disorder is Tic/Tourette's        disorder.    -   (8) The use according to the above (2), wherein the behavioral        disorder is Tic/Tourette's disorder:    -   (9) The therapeutic agent for a behavioral disorder according to        the above (3), wherein the behavioral disorder is Tic/Tourette's        disorder.

Tic/Tourette's disorder includes Tourette's disorder, chronic motor orvocal tic disorder, transient tic disorder, and tic disorder nototherwise specified.

The pharmaceutically acceptable salts of Compound (I) includepharmaceutically acceptable acid addition salts, metal salts, ammoniumsalts, organic amine addition salts and amino acid addition salts.

The pharmaceutically acceptable acid addition salts of Compound (I)include inorganic acid addition salts such as hydrochloride, sulfate andphosphate, and organic acid addition salts such as acetate, maleate,fumarate, tartrate, citrate and methanesulfonate; the pharmaceuticallyacceptable metal salts include alkali metal salts such as sodium saltand potassium salt, alkaline earth metal salts such as magnesium saltand calcium salt, aluminum salt, and zinc salt; the pharmaceuticallyacceptable ammonium salts include ammonium and tetramethylammonium; thepharmaceutically acceptable organic amine addition salts include saltswith morpholine and piperidine; and the pharmaceutically acceptableamino acid addition salts include salts with lysine, glycine andphenylalanine.

Compound (I) can be produced by the method disclosed in JapanesePublished Unexamined Patent Application No. 211856/94, JapanesePublished Unexamined Patent Application No. 16559/94 or WO 94/01114, oraccording to these methods. The desired compound in the process can beisolated and purified by purification methods conventionally used insynthetic organic chemistry, such as filtration, extraction, washing,drying, concentration, recrystallization or various kinds ofchromatography.

In the case where a salt of compound (I) is desired and it is producedin the form of a desired salt, it may be subjected to purification assuch. In the case where compound (I) is produced in the free form andits salt is desired, it is dissolved or suspended in a suitable solvent,and then an acid or a base may be added thereto to form the salt.

Compound (I) and pharmaceutically acceptable salts thereof may be in theform of adducts with water or various solvents, which can satisfactorilybe used in the method or the use, or as the therapeutic agent of thepresent invention.

The physicochemical data of Compound (I) are described below.

Compound 1:

Melting point: 190.4-191.3° C. Elemental analysis: C₂₀H₂₄N₄O₄ Calcd.(%): C 62.48, H 6.29, N 14.57 Found (%): C 62.52, H 6.53, N 14.56 IR(KBr) νmax (cm⁻¹): 1697, 1655, 1518 NMR (CDCl₃, 270 MHz) δ(ppm): 7.74(1H, d, J=15.5 Hz), 7.18 (1H, dd, J=8.3, 1.9 Hz), 7.08 (1H, d, J=1.9Hz), 6.89 (1H, d, J=8.3 Hz), 6.77 (1H, d, J=15.5 Hz), 4.21 (2H, q, J=6.9Hz), 4.09 (2H, q, J=6.9 Hz), 4.06 (3H, s), 3.96 (3H, s), 3.93 (3H, s),1.39 (3H, t, J=6.9 Hz), 1.27 (3H, t, J=6.9 Hz)

A striking feature of ADHD is the unusual response to stimulantmedication. Thus, administration of amphetamine to children with ADHDresults in a sharp decrease in motor activity. Since the usualpharmacological response to amphetamine is an increase in motoractivity, this response has been termed “paradoxical”. In rat pupstreated with 6-hydroxydopamine, administration of methamphetaminereduces the hyperactivity, an effect paralleling the paradoxicalresponse to the agent in ADHD. Accordingly, 6-hydroxydopamine-treatedrat pups are an accepted model for ADHD in humans [Nature, 264, pp.153-155 (1976)].

The pharmacological actions of Compound (I) are described in testexamples.

TEST EXAMPLE 1 Effect of Compound (I) on Locomotor Activity in6-Hydroxydopamine-Treated Neonatal Rats

Methods: Female neonatal SD rats were used for the experiments. 100 μg6-Hydroxydopamine (6-HODA) was dissolved in a 0.1% solution of ascorbicacid in saline, and the obtained solution or 0.1% ascorbic acid insaline (control) was injected first at 3 days of age into the leftlateral ventricle of the rat and secondly at 6 days of age into theright lateral ventricle of the rat. At 30-37 days, locomotor activitywas measured by placing the rat in a transparent acrylic box (50×50×50cm) 60 minutes after the drug administration using digital counters withinfrared sensors (Scanet MV-10MT; Toyo Sangyo Co. Ltd., Toyama, Japan).

Compound (I) was suspended in a 0.3% aqueous Tween 80 solution, andadministered orally to 6-HODA treated rats.

Results: The intracerebroventricular administrations of 6-HODA to pupsresulted in increase of locomotor activity compared with vehicletreatment control. Compound (I), administered orally at 1.25 mg/kg and 5mg/kg to 6-HODA treated rats, decreased locomotor activities, whereas itincreased locomotor activities of control rats treated only with 0.1%ascorbic acid in saline, vehicle.

The results are shown in FIG. 1.

The above results indicate that Compound (I) is effective for improvingADHD.

TEST EXAMPLE 2 Effect of Compound (I) on Tic/Tourette Like Symptoms in6-Hydroxydopamine-Treated Young Rats

Methods: 6-HODA was injected into the left medial forebrain bundle of arat to induce a unilateral lesion of dopaminergic neurons, followed byrepeated oral administration of L-DOPA at 20 mg/kg twice daily for 2weeks to make a rat model of tic-like symptoms.

Tic-like, abnormal involuntary movements were observed after day 3during repetitive treatment with L-DOPA. Two subtypes of involuntarymovements were classified as axial (lateral torsion of the head, neckand trunk towards the side contralateral to the lesion, including swingof the head) and forelimb (abnormal movements contralateral to thelesion, including kicking movements of the forelimb).

The severity of these movements was assigned a score from 0 to 4 to eachmovement as follows.

Axial

(score 0) no deviation of head

(score 1) lateral deviation of head: 30° or less

(score 2) lateral deviation of head: more than 30°, and 60° or less

(score 3) torsion of head and upper trunk: more than 60°, and 90° orless

(score 4) torsion of head and trunk: more than 90°

Forelimb

(score 0) no movements of both distal and proximal forelimbs

(score 1) tiny oscillatory movements of the distal forelimb

(score 2) movements of low amplitude but causing visible translocationof both distal and proximal forelimbs

(score 3) translocation of the whole limb with visible contraction ofshoulder muscles

(score 4) vigorous limb and shoulder movements of maximal amplitude

Compound (I) was repeatedly administered orally to 6-HODA treated ratsat 1 mg/kg for 23 days, and Tic-like, abnormal involuntary movementswere observed every 10 minutes for 3-hours, each time for one minute.

Peak score was obtained by adding the peak score for forelimb to thatfor axial (Data are expressed as mean ± standard deviation in thefollowing Table 1). Peak time means the time after the firstadministration when peak score was observed.

Results: Compound (I), administered orally at 1 mg/kg, decreased peakscore and peak time compared with those before administration ofCompound (I).

The results are shown in Table 1. TABLE 1 EFFECTS OF SUBSTANCE ONTIC/TOURETTE LIKE SYMPTOMS IN 6-HYDROXYDOPAMINE-TREATED YOUNG RATSTreatment (mg/kg) peak score p.o. −60 min (n = 6) peak time (min)Pre-treatment 7.0 ± 1.0 110 L-DOPA + Day 1 5.6 ± 1.4 30 Compound (I) Day9 4.4 ± 1.6 40 (1 mg/kg) Day 23 1.6 ± 0.6 20

The above results indicate that Compound (I) is effective for improvingTic/Tourette's disorder.

TEST EXAMPLE 3 Effect of Compound (I) on the Acquisition of a DelayedAlternation Task in the Young Rats

The following experiment was carried out according to a method describedin Drug Dev. Res., 35, p. 83-95 (1996) with a slight modification.

Methods: Male Rj: Wistar (Han) rats were used for the experiments.Before being tested, the rats were given the standard diet each day.Several 45 mg food pellets (these were also used in the delayedalternation sessions described below) were also given them to habituatethem to this novel food.

The aim of this phase is to train rats, on the presentation of a singlecentralized retractable lever, to press on it to receive a food pellet.

The rats were subjected to 10 lever-pressing acquisition sessions in theexperimental chambers according to a fixed ratio (FR1) schedule ofreinforcement. Reinforcement consists of food pellets (45 mg) deliveredafter each lever-press. Each daily session lasts 15 minutes. All ratsreceived an intraperitoneal administration of physiological saline 30minutes before each session. During the first 7 sessions, the Skinnerboxes were equipped with only one fixed lever situated centrally abovethe food receptacle, to avoid spatial preference for the right or theleft side of the experimental panel. After the 7th lever-pressingsession, the boxes were equipped with two retractable levers located oneither side of the food receptacle. The rats were then subjected to 3consecutive sessions in which the left or the right lever waspseudo-randomly presented every 5 seconds. At the end of this phase 80to 100% of the rats acquired the lever press-response. Rats which failedto learn were excluded from the experiments. If some rats were close toestablishing steady lever-pressing behavior they were given extratraining with the aim of attaining at least 10 rats per group. Rats wereassigned to treatment groups matched on the basis of their performance.

Subsequent to lever-press acquisition sessions, all rats were subjectedto delayed alternation sessions. The test was conducted for 5 days.During this phase, the boxes were equipped with two retractable leverson each side of the food distributor. Each session consisted of 35successive trials every 10 seconds. In each trial, the rat was firstpresented with one lever (left or right). When the rat pressed on thelever, the rat was given a food pellet, the lever was retracted and 5seconds later two levers were presented. The rat had to learn to presson the lever opposite to that previously presented to gain a food pellet(non-matching to sample). If the rat did not respond to a one- ortwo-lever presentation within 20 seconds, the lever(s) were withdrawnand the next trial commenced 10 seconds later.

Compound (I) was suspended in 0.5% methylcellulose in distilled waterand administered orally 60 minutes before each session.

The effect of Compound (I) was evaluated by measuring simple reactiontime, which means the reaction time to each one-lever presentation, andchoice reaction time, which means the reaction time to each two-leverpresentation.

Results:

(Simple Reaction Time)

Compound (I), administered orally at 0.3 mg/kg, significantly decreasedsimple reaction times compared with those obtained in control ratstreated only with 0.5% methylcellulose, vehicle.

The results are shown in Table 2-A. TABLE 2-A EFFECTS OF SUBSTANCE ONSIMPLE REACTION TIMES OF YOUNG RATS IN THE DELAYED ALTERNATIONACQUISITION TEST Simple reaction times per session (seconds) Treatment(mg/kg) (mean ± s.e.m.) p.o. −60 min S1 S2 S3 S4 S5 Vehicle 4.56 ± 0.343.53 ± 0.29 2.68 ± 0.28 2.06 ± 0.20 2.01 ± 0.22 KW-6002 3.16 ± 0.24 2.49± 0.28 1.83 ± 0.20 1.73 ± 0.21 1.33 ± 0.11 0.3 ** * * NS *Student's t test:NS = Not Significant;* = p < 0.05;** = p < 0.01

The above results indicate that Compound (I) is effective for improvingADHD.

(Choice Reaction Time)

Compound (I), administered orally at 0.3 mg/kg, significantly decreasedchoice reaction times compared with those obtained in control ratstreated only with 0.5% methylcellulose, vehicle.

The results are shown in Table 2-B. TABLE 2-B EFFECTS OF SUBSTANCE ONCHOICE REACTION TIMES OF YOUNG RATS IN THE DELAYED ALTERNATIONACQUISITION TEST Choice reaction times per session (seconds) Treatment(mg/kg) (mean ± s.e.m.) p.o. −60 min S1 S2 S3 S4 S5 Vehicle 2.26 ± 0.221.99 ± 0.20 1.57 ± 0.19 1.16 ± 0.12 1.27 ± 0.16 KW-6002 1.71 ± 0.13 1.52± 0.10 1.22 ± 0.12 1.13 ± 0.18 0.92 ± 0.09 0.3 * * NS NS NSStudent's t test:NS = Not Significant;* = p < 0.05

The above results indicate that Compound (I) is effective for improvingADHD.

TEST EXAMPLE 4 Acute Toxicity Test

Compound (I), was orally or intraperitoneally administered to groups ofdd-strain male mice weighing 20±1 g, each group consisting of threemice. Seven days after the administration, the mortality was observed todetermine a minimum lethal dose (MLD) of Compound (I).

The MLD value of Compound (I) was greater than 1000 mg/kg for oraladministration.

Compound (I) or pharmaceutically acceptable salts thereof can be used assuch or in the form of various pharmaceutical compositions. Thepharmaceutical compositions of the present invention can be prepared byuniformly mixing an effective amount of compound (I) or apharmaceutically acceptable salt thereof as an active ingredient withpharmaceutically acceptable carriers. The pharmaceutical compositionsare preferably in a unit dosage form suitable for rectal administration,oral or parenteral (including subcutaneous, intravenous andintramuscular administration) administration, etc.

For preparing a pharmaceutical composition for oral administration, anyuseful pharmaceutically acceptable carriers can be used. For example,liquid preparations for oral administration such as suspension and syrupcan be prepared using water; sugars such as sucrose, sorbitol andfructose; glycols such as polyethylene glycol and propylene glycol; oilssuch as sesame oil, olive oil and soybean oil; preservatives such as ap-hydroxybenzoate; flavors such as strawberry flavor and peppermint,etc. Powder, pills, capsules and tablet scan be prepared usingexcipients such as lactose, glucose, sucrose and mannitol;disintegrating agents such as starch and sodium alginate; lubricantssuch as magnesium stearate and talc; binders such as polyvinyl alcohol,hydroxypropyl cellulose and gelatin; surfactants such as fatty acidesters; plasticizers such as glycerin, etc. Tablets and capsules are themost useful oral unit dosage because of the readiness of administration.For preparing tablets and capsules solid pharmaceutical carriers areused.

Injectable preparations can be prepared using carriers such as distilledwater, a salt solution, a glucose solution and a mixture of a saltsolution and a glucose solution. The preparation can be prepared in theform of solution, suspension or dispersion according to a conventionalmethod by using a suitable auxiliary.

Compound (I) or a pharmaceutically acceptable salt thereof can beadministered orally in the pharmaceutical form described above orparenterally as the injection. The effective dose and administrationschedule vary depending on the mode of administration, age, weight, andsymptoms of a patient, etc. However, generally, compound (I) or apharmaceutically acceptable salt thereof is administered in a dose of 1to 900 mg/60 kg/day, preferably in a dose of 1 to 200 mg/60 kg/day.

Certain embodiments of the present invention are described in thefollowing examples.

EXAMPLE 1 Tablets

Tablets having the following composition were prepared in a conventionalmanner.

Compound (I) (40 g) was mixed with 286.8 g of lactose and 60 g of potatostarch, followed by addition of 120 g of a 10% aqueous solution ofhydroxypropyl cellulose. The resultant mixture was kneaded, granulated,and then dried by a conventional method. The granules were refined togive granules used to make tablets. After mixing the granules with 1.2 gof magnesium stearate, the mixture was formed into tablets eachcontaining 20 mg of the active ingredient by using a tablet maker (ModelRT-15, Kikusui) having pestles of 8 mm diameter.

The prescription is shown in Table 3. TABLE 3 Compound (I) 20 mg Lactose143.4 mg Potato Starch 30 mg Hydroxypropyl Cellulose 6 mg MagnesiumStearate 0.6 mg 200 mg

EXAMPLE 2 Capsules

Capsules having the following composition were prepared in aconventional manner.

Compound (I) (200 g) was mixed with 995 g of Avicel and 5 g of magnesiumstearate. The mixture was put in hard capsules No. 4 each having acapacity of 120 mg by using a capsule filler (Model LZ-64, Zanashi) togive capsules each containing 20 mg of the active ingredient.

The prescription is shown in Table 4. TABLE 4 Compound (I) 20 mg Avicel99.5 mg Magnesium Stearate 0.5 mg 120 mg

EXAMPLE 3 Injections

Injections having the following composition were prepared in aconventional manner.

Compound (I) (1 g) was dissolved in 100 g of purified soybean oil,followed by addition of 12 g of purified egg yolk lecithin and 25 g ofglycerin for injection. The resultant mixture was made up to 1,000 mlwith distilled water for injection, thoroughly mixed, and emulsified bya conventional method. The resultant dispersion was subjected to asepticfiltration by using 0.2 μm disposable membrane filters, and thenaseptically put into glass vials in 2 ml portions to give injectionscontaining 2 mg of the active ingredient per vial.

The prescription is shown in Table 5. TABLE 5 Compound (I) 2 mg PurifiedSoybean Oil 200 mg Purified Egg Yolk Lecithin 24 mg Glycerine forInjection 50 mg Distilled Water for Injection 1.72 ml 2.00 ml

1. A method of treating a behavioral disorder, comprising administeringan effective amount of (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine or apharmaceutically acceptable salt thereof to a patient in need thereof.2. Use of (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine or apharmaceutically acceptable salt thereof for manufacturing a therapeuticagent for the treatment of a behavioral disorder.
 3. A therapeutic agentfor a behavioral disorder comprising(E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methylxanthine or apharmaceutically acceptable salt thereof.
 4. The method of treating abehavioral disorder according to claim 1, wherein the behavioraldisorder is attention deficit hyperactivity disorder.
 5. The useaccording to claim 2, wherein the behavioral disorder is attentiondeficit hyperactivity disorder.
 6. The therapeutic agent for treating abehavioral disorder according to claim 3, wherein the behavioraldisorder is attention deficit hyperactivity disorder.
 7. The method oftreating a behavioral disorder according to claim 1, wherein thebehavioral disorder is Tic/Tourette's disorder.
 8. The use according toclaim 2, wherein the behavioral disorder is Tic/Tourette's disorder. 9.The therapeutic agent for treating a behavioral disorder according toclaim 3, wherein the behavioral disorder is Tic/Tourette's disorder.